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新生大鼠给予氟伏沙明对其身体发育及5-羟色胺能系统活性的影响。

Effects of neonatal fluvoxamine administration on the physical development and activity of the serotoninergic system in white rats.

作者信息

Glazova N Yu, Merchieva S A, Volodina M A, Sebentsova E A, Manchenko D M, Kudrun V S, Levitskaya N G

机构信息

Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov Sq., 2, 123182 Moscow, Russia.

Biological Faculty, Lomonosov State University, Moscow, Leninskie Gory, 1/12, Russia.

出版信息

Acta Naturae. 2014 Jul;6(3):98-105.

Abstract

Selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, are widely used to treat depressive disorders in pregnant women. These antidepressants effectively penetrate through the placental barrier, affecting the fetus during the critical phase of neurodevelopment. Some clinical studies have linked prenatal exposure to SSRIs with increased neonatal mortality, premature birth, decreased fetal growth and delay in psychomotor development. However, the effects of prenatal exposure to SSRIs remain unknown. The administration of SSRIs in rodents during the first postnatal weeks is considered as an model for studying the effects of prenatal SSRIs exposure in human. The aim of this work was to study the acute effects of chronic fluvoxamine (FA) administration in white rat pups. The study was carried out in male and female rat pups treated with FA (10 mg/kg/day, intraperitoneally) from postnatal days 1 to 14. The lethality level, body weight, age of eye opening, and motor reflex maturation were recorded. The contents of biogenic amines and their metabolites in different brain structures were also determined. It was shown that neonatal FA administration led to increased lethality level, reduced body weight, and delayed maturation of motor reflexes. Furthermore, increased noradrenalin level in hypothalamus, serotonin level in hippocampus and serotonin metabolite 5-HIAA level in frontal cortex, hypothalamus, hippocampus, and striatum were observed in drug-treated animals compared to the control group. We can conclude that the altered activity of the serotoninergic system induced by fluvoxamine administration at early developmental stages leads to a delay in physical and motor development.

摘要

选择性5-羟色胺再摄取抑制剂(SSRI),包括氟伏沙明,被广泛用于治疗孕妇的抑郁症。这些抗抑郁药能有效穿透胎盘屏障,在神经发育的关键阶段影响胎儿。一些临床研究将产前接触SSRI与新生儿死亡率增加、早产、胎儿生长发育迟缓以及精神运动发育延迟联系起来。然而,产前接触SSRI的影响仍不明确。在出生后第一周给啮齿动物施用SSRI被认为是研究人类产前接触SSRI影响的一种模型。这项工作的目的是研究慢性给予氟伏沙明(FA)对白鼠幼崽的急性影响。该研究在出生后第1天至14天接受FA(10毫克/千克/天,腹腔注射)治疗的雄性和雌性大鼠幼崽中进行。记录了致死率水平、体重、睁眼年龄和运动反射成熟情况。还测定了不同脑结构中生物胺及其代谢物的含量。结果表明,新生大鼠给予FA会导致致死率水平升高、体重减轻和运动反射成熟延迟。此外,与对照组相比,在接受药物治疗的动物中观察到下丘脑去甲肾上腺素水平升高、海马体5-羟色胺水平升高以及额叶皮质、下丘脑、海马体和纹状体中5-羟色胺代谢物5-羟吲哚乙酸水平升高。我们可以得出结论,在发育早期给予氟伏沙明引起的5-羟色胺能系统活性改变会导致身体和运动发育延迟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f6/4207564/6d251579f7b0/AN20758251-22-098-g001.jpg

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